Intravenous Gammaglobulin for Sickle Cell Pain Crises

Condition(s) targeted: Sickle Cell Anemia

Intervention: Immune Globulin Intravenous (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Shi, Patricia, M.D.

Official(s) and/or principal investigator(s):
Patricia A Shi, MD, Principal Investigator, Affiliation: Mount Sinai School of Medicine

Overall contact:
Patricia A Shi, MD, Phone: 212-241-9237, Email: patricia.shi@mssm.edu

The purpose of this study is to determine whether intravenous immune globulin is safe and effective in the acute treatment of pain crises in sickle cell disease.

Official title: Treatment of Sickle Cell Vaso-Occlusive Crises With High-Dose Intravenous Gammaglobulin

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Duration of pain crisis

Secondary outcome:

Total opioid use

Length of hospitalization

Detailed description: This is a randomized, double-blind, placebo-controlled, dose-escalation Phase I-II trial to study the safety and efficacy of a single dose of IVIG compared to normal saline placebo administered to patients with sickle cell anemia admitted to the hospital with an uncomplicated acute pain episode. A total of 56 subjects will be enrolled. The hypothesis is that IVIG will act quickly to reduce vaso-occlusion and thus pain scores, narcotic use, and length of hospitalization. The physiological effects of IVIG in patients with sickle cell disease will also be evaluated by measuring the adhesion receptors involved in leukocyte adherence to endothelium and red blood cell-leukocyte interactions, microcirculatory blood flow, and serum markers of hemolysis.

Minimum age: 8 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Documented diagnosis of sickle cell disease (SS or S-β thalassemia genotype)

- Age 8-65 years

- Uncomplicated acute pain episode requiring hospital admission and parenteral

narcotics

Exclusion Criteria:

- Increased stroke risk as assessed by transcranial Doppler or magnetic resonance

imaging (all subjects undergo testing)

- Concomitant acute process, including fever > 38. 5° C with clinical suspicion of

infection

- Increased ALT > 2X ULN

- Serum creatinine ≥1. 3 mg/dL, >300 mg/dL protein in spot urinalysis, or known

condition associated with renal dysfunction

- Hb > 10 g/dL and Hct > 30%

- IgA deficiency or known allergy to gamma globulin

- Pregnancy or breastfeeding

- Vaccination with a live attenuated virus in the preceding 6 weeks

- Documented history of illicit (eg. heroin, cocaine) drug abuse or drug-seeking

behavior

- Current participation in another investigational drug study

- Previous participation in this study within last 3 months

- Current treatment with chronic transfusion

Patricia A Shi, MD, Phone: 212-241-9237, Email: patricia.shi@mssm.edu

Montefiore Medical Center, Bronx, New York 10461, United States; Recruiting
Deepa Manwani, MD, Phone: 718-741-2342, Email: dmanwani@montefiore.org
Karen Ireland, BS, Phone: 718-741-2401, Email: kireland@montefiore.org
Deepa Manwani, MD, Principal Investigator
Larry Cytryn, MD, Sub-Investigator

Mount Sinai School of Medicine, New York, New York 10029, United States; Recruiting
Patricia A. Shi, MD, Phone: 212-241-9237, Email: patricia.shi@mssm.edu
Josella Aguilar, RN, Phone: 212-824-7375, Email: josella.aguilar@mssm.edu
Patricia A Shi, MD, Principal Investigator
Paul S Frenette, MD, Sub-Investigator

Related publications:

Chang J, Shi PA, Chiang EY, Frenette PS. Intravenous immunoglobulins reverse acute vaso-occlusive crises in sickle cell mice through rapid inhibition of neutrophil adhesion. Blood. 2008 Jan 15;111(2):915-23. Epub 2007 Oct 11.

Turhan A, Jenab P, Bruhns P, Ravetch JV, Coller BS, Frenette PS. Intravenous immune globulin prevents venular vaso-occlusion in sickle cell mice by inhibiting leukocyte adhesion and the interactions between sickle erythrocytes and adherent leukocytes. Blood. 2004 Mar 15;103(6):2397-400. Epub 2003 Nov 20.

Starting date: November 2008
Last updated: September 26, 2011